Data continue to accumulate supporting the hypothesis that circulating estrogens may function as promotor agents during the development of endometrial cancer in postmenopausal women. The theme of this research proposal is to comprehensively examine the role of circulating estrogens in this process. The presence of estrogens in the circulation of postmenopausal women will be defined in terms of biological as well as immunological activity. The in vivo transport of circulating estrogens into the uterus will be determined. The intracellular metabolism of circulating estrogens by endometrial cells and the influence of this metabolism on nuclear binding of these hormones will be determined. The actions of circulating estrogens on endometrial cell function will be evaluated using promotion of cellular growth and protein synthesis (progesterone receptors) as markers of estrogenic activity. These studies will be performed using blood and endometrial tissue samples from postmenopausal women at low risk (slender women, not on estrogen replacement) and at high risk (obese women) for the development of this tumor and from patients who have the disease. These studies should comprehensively define the role of circulating estrogens in the development of this tumor in terms of presently available techniques.